1. Field of the Invention
This invention relates to a process for the synthesis of indoles by dehydrogenation, preferably catalytic dehydrogenation, of indolines.
2. Statement of Related Art
Indoles are of considerable significance in the fields of pharmacy, cosmetics and dyeing.
The most important process for the synthesis of indole derivatives is Fischer's indole synthesis. In this process, the corresponding indole derivative is formed from the phenyl hydrazone of a keto compound by Diaza-Cope rearrangement and subsequent elimination of ammonia. Unfortunately, this process cannot be universally used and, above all, cannot be used when there are additional substituents at the aromatic 6-ring. The synthesis of 5,6-dihydroxyindoles is particularly difficult because 5,6-dihydroxyindoles are highly sensitive to oxidation on account of their inherent double hydroquinone structure. Their synthesis requires other processes which may be divided into three groups namely:
formation of the 5,6-dihydroxyindole skeleton by reductive cyclization of suitable nitrobenzene precursors (B. P. Murphy, T. M. Schultz, J. Org. Chem. 50 (1985) 2790),
formation of the 5,6-dihydroxyindole skeleton by oxidative cyclization of catecholamines (J. D. Bu'Lock, J. Marley-Mason, J. Chem. Soc. (1951) 2248; J. Marley-Mason, J. D. Bu'Lock, Nature 166 (1950) 1036; K. Wakamatsu, S. Ito, Anal. Biochem. 170 (1988) 335; P. A. Wehrli, F. Pigott, U. Fischer, A. Kaiser, Helv. Chim. Acta 55 (1972) 3057 and J. Harley-Mason, J. Chem. Soc. (1953) 200),
elimination of 5,6-dihydroxyindoles from 5,6-dialkoxy or 5,6-diacetoxy indoles (R. J. S. Beer, K. Clarke, H. E. Khorana, A. Robertson, J. Chem. Soc. (1948) 2223; H. Burton, J. A. Duffield, P. F. G. Praill, J. Chem. Soc. (1950) 1062; J. D. Benigni, R. L. Minnis, J. Heterocycl. Chem. 2 (1965) 387 and DE-A1-37 37 825).
The disadvantages of these processes lie in the poor yields and complicated purification measures or in complicated syntheses and high prices of the starting materials.
Accordingly, there is a need for a universally usable process for the production of indole derivatives, especially the sensitive 5,6-dihydroxyindole derivatives, in which the products could be obtained in high yields and purity from a readily accessible precursor in a smooth reaction.
It has now surprisingly been found that indoles can readily be obtained by dehydrogenation of the corresponding readily accessible indolines.